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Viagra and Oxytocin

Articles in the press recently reported that Viagra increases oxytocin. Here's the press release posted by University of Wisconsin-Madison, which is also reproduced below in a footnote.1 We were intrigued by that claim and did a little digging into the latest research ourselves.

First, here's a some background, which regular visitors to this site may already be familiar with. Oxytocin has many functions in the body, depending upon where it is released and to which nerve cell receptors it binds, and depending upon what else is going on in the body. Although it is called the “cuddle or bonding” hormone, bonding generally doesn't happen unless it is released in a very specific part of the brain.

When it rises elsewhere in the brain, or out in the body, that is, in the blood, where it is obviously a lot easier to measure, it appears to be doing quite different tasks from the task of bonding. For example, it is necessary for men to experience erections, it is believed by some researchers to cause the contractions associated with orgasm, it causes labor contractions in women about to give birth, and so forth. In those instances it isn't necessarily causing bonding, although in the case of birth, it appears that oxytocin is also released in the brain to bond mothers with their infants.

Higher levels of oxytocin in the blood have been associated with better health, more rapid healing, and, paradoxically, with intense relationship upset in women. Again, it is not apparent that these higher levels of oxytocin in the blood directly induce bonding, although in a rodent experiment, repeated physical stimulation did seem to trigger changes that suggested oxytocin was being released in the bonding part of the brain, too.

Scientists believe that oxytocin must be released in a very specific part of the brain for it to encourage monogamy and bonding. They discovered this by examining the brains of mating voles, and noting the differences in oxytocin levels between the brains of monogamous and promiscuous species. Experts surmise that this release of oxytocin in the bonding area of the brain creates the phenomenon of parents bonding with their kids, and is behind friendships as well as bonding in intimate relationships. In short, we couldn't fall in love without this neurochemical being released in this very specific part of our brains.

Because the process of releasing oxytocin in the brain is so subtle, and easily influenced by other emotions (and their associated neurochemicals), we can't simply dose ourselves with oxytocin to create a lasting emotional bond. Even so, some vendors are trying to sell people nasal sprays with that goal, as well as air sprays to encourage unsuspecting partners to fall in love. (See "Liquid Love".) Nasal sprays containing oxytocin – and Viagra itself - have been shown to be risky in the past, but that isn't stopping today's pharmaceutical vendors.

Back to the Viagra experiment

The Viagra study itself did not find that Viagra increased the release of oxytocin in the brain...except when electrical stimulation was applied to the subjects' pituitaries. In short, it was the electrical stimulation that triggered the actual release of the oxytocin in the animals given Viagra.

So unless you plan to use Viagra with pulsing electrodes in your brain, you needn't concern yourself with taking it to increase emotional bonding with a partner. Also, although the oxytocin released in this experiment was released in the brain, it wasn't measured in the part of the brain that has been shown to induce bonding. Rather, the increase was measured in the area of the pathway that is associated with levels of oxytocin in the blood. In short, the oxytocin released may have been related strictly to a job out in the body, such as erection, or perhaps ejaculation, rather than emotional bonding.

Incidentally, oxytocin is critical to erection. Another recent experiment showed that oxytocin injected into the area of the brain stimulated in the Viagra experiment induces erection (and fires up the nearest dopamine-receptor-rich neurons).

Scientists are intrigued by the Viagra experiment not because they think it proves Viagra leads to emotional bonding, but because it may suggest that Viagra causes more than erections. It may have other, as yet unknown, effects on the brain. These additional effects may lead to expensive new drugs based on Viagra, but with other names and other indications. However, it's not likely that those Viagra-based products will be prescribed for emotional bonding.

MADISON - The little blue pill may do more than get the blood pumping. Sildenafil - the generic name for Viagra - also increases release of a reproductive hormone in rats, according to a new study.

Researchers at the University of Wisconsin-Madison report this month that sildenafil increases the amount of oxytocin released by stimulation of the posterior pituitary gland, a small structure directly underneath the brain that regulates hormone levels in response to neural signals.

The finding is the first indication of a chemical mechanism through which erectile dysfunction drugs like Viagra may have physical effects besides increasing blood flow to sexual organs, says study author Meyer Jackson, a physiology professor at the UW-Madison School of Medicine and Public Health.

Sometimes called the "love hormone" or "cuddle chemical," oxytocin plays several important roles in social interactions and reproduction, including triggering uterine contractions and lactation. It is also released during orgasm and has been linked to sexual arousal.

Oxytocin release is regulated by an enzyme that acts like a braking system, limiting hormone release by dampening neural excitation of the cells. This same enzyme, phosphodiesterase type 5, also limits blood flow by contracting the muscles around blood vessels.

In both places, sildenafil works by blocking this enzyme, essentially releasing the brakes, explains Jackson. In blood vessels, relaxing smooth muscle increases blood flow, which corrects erectile dysfunction, and in the posterior pituitary, the cells become more responsive. "The same stimulation will produce more [oxytocin] release."

He says, "I think this is a missing link in terms of trying to sort out the issues around whether there are additional effects of phosphodiesterase type 5 inhibitors," which include Viagra, Levitra and Cialis.

The new report was published online Aug. 9 and appears in an upcoming issue of the Journal of Physiology.

In the study, the scientists measured oxytocin released from rat pituitaries in response to neural stimulation. When the pituitaries were treated with sildenafil, they responded to the stimulation by releasing three times as much oxytocin as they did without the drug.

Importantly, the drug had little if any effect on hormone release in the absence of stimulation, Jackson says.

"Erectile dysfunction drugs do not induce erections spontaneously, they enhance the response to sexual stimulation," he says. "The same thing is happening in the posterior pituitary - Viagra will not induce the release of oxytocin on its own, but it will enhance the amount of release you get in response to electrical stimulation."

Though he doesn't think his findings raise any significant safety issues related to Viagra use, he does think it provides strong rationale for studies of additional effects and new potential uses.

"A big question raised by our study is, will sildenafil do the same thing to the nerve terminals that release oxytocin [in the brain]?" he says. The cells that supply oxytocin to the pituitary come from a brain structure called the hypothalamus, which also sends hormones throughout the brain.

Though sildenafil's effects on these pathways are still unknown, work by other researchers has shown that oxytocin-sensitive cells in the brain play a role in the neural control of erectile responses, suggesting that Viagra and its kin may work through multiple channels.

The famous blue pills could have other uses as well. Oxytocin has been linked to the ability to make strong social bonds, while sildenafil was recently shown to improve hamsters' abilities to adjust the timing of their internal clocks to overcome simulated jet lag.

"This is one piece in a puzzle in which many pieces are still not available," Jackson says. "But it raises the possibility that erectile dysfunction drugs could be doing more than just affecting erectile dysfunction."